Brain edemas means such a state of the brain that water in a living body has unusually accumulated inside of the brain parenchyma to increase the volume of the brain tissue. As for the factors inducing brain edemas, for example, cerebrovascular diseases such as stroke, head injury, brain tumor, hypertension, respiratory insufficiency, CO poisoning, hyponatremia, acute nephropathy, disequilibrium syndrome caused by hemodialysis, hyperglycemia, hypoglycemia, adrenal insufficiency, collagen diseases, and tin, lead or arsenical poisoning are exemplified. Particularly, a treatment of brain edemas which are caused in an acute phase of stroke or by head injury is a very important problem to be solved. Furthermore, brain edemas are likely to cause a cerebral cerebral hernia, a headache, nausea, vomiting, restless, convulsions, clouding of consciousness and the like. Particularly, a deterioration of a cerebral hernia sometimes causes the patients to die.
Brain edemas are classified into cytotoxic edemas, vasogenic edemas and the like according to the mechanisms of the occurrence, but these types of edemas often appear together, and so the etiology of brain edemas has not been clear enough. It is desired to make the etiology clear and establish the method for the treatment.
Currently, hyperosmotic medicaments or adrenocortical steroids and the like have been used for treating brain edemas.
As hyperosmotic medicaments, 10% glycerol, 5% fructose-added physiological saline, 15% or 20% mannitol and the like may be exemplified. Intravenous administration of these hypertonic medicaments raises blood osmotic pressure to produce a difference of the pressure between the brain parenchyma tissues and the blood; as a result water accumulated in the brain tissues moves into the bloodstream to improve brain edemas. Furthermore, these medicaments are characterized by slight side effects since they scarcely pass through the blood brain barrier to reach the brain parenchyma tissues. But even for these medicaments, the accumulation in a brain in some degree cannot entirely be avoided, when the blood concentration reach high by a large quantity administration. In case a blood brain barrier is injured, the medicaments easily move to the brain; if the blood concentration of the medicaments decreases after stopping to administer the medicaments and the osmotic pressure in the brain tissue becomes higher than that in the blood, water in the blood could move back to the brain parenchyma tissue and brain edemas might appear again. These medicaments also have side effects such as electrolytic aberration, nephropathy and the like.
As for adrenocortical steroids, dexamethasone, hydrocortisone and the like are exemplified. These adrenocortical steroids exhibit ameliorative effects on brain edemas around brain tumors, but these have little effects on ischemic and traumatic brain edemas and exhibit side effects such as digestive tract hemorrhage, infectious disease exacerbation, diabetes exacerbation and the like.
Recently, calcium antagonists such as Nimodipine, Nicardipine, NC-1100 and the like have attracted attention as alternative medicaments for treating brain edemas. It is reported that the pretreatment with these calcium antagonists delays the progress of cellular brain edemas. MK-801, a glutamate antagonist, is also known to exhibit an inhibitory effect on brain edemas. These calcium antagonists and glutamate antagonists which have inhibitory effects on brain edemas, however, have not yet been used clinically.